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Characterization of monoclonal antibodies against foot-and-mouth disease virus serotype O and application in identification of antigenic variation in relation to vaccine strain selection.

Yang M, Xu W, Goolia M, Zhang Z - Virol. J. (2014)

Bottom Line: Isolates ECU/4/10 and HKN/2/11 demonstrated the highest antigenic variation compared to the others.The amino acid sequences of the outer capsid proteins for these nine isolates were analyzed and compared with the vaccine strain O1/Manisa.However, for vaccine matching VNT remains the preferred method but a combination of VNT, antigenic profiling with a panel of mAbs and genetic sequencing would probably be more ideal for full characterization of any new outbreak isolates as well as for selection of vaccine strains from FMDV antigen banks.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Centre for Foreign Animal Disease, 1015 Arlington Street, Winnipeg R3E 3 M4, Manitoba, Canada. Ming.Yang@inspection.gc.ca.

ABSTRACT

Background: Foot-and-mouth disease (FMD) has severe implications for animal farming which leads to considerable financial losses because of its rapid spread, high morbidity and loss of productivity. For these reasons, the use of vaccine is often favoured to prevent and control FMD. Selection of the proper vaccine is extremely difficult because of the antigenic variation within FMDV serotypes. The aim of the current study was to produce a panel of mAbs and use it for the characterization of new isolates of FMDV serotype O.

Results: A panel of FMDV/O specific mAb was produced. The generated mAbs were then characterized using the peptide array and mAb resistant mutant selection. Seven out of the nine mAbs reacted with five known antigenic sites, thus the other two mAbs against non-neutralizing sites were identified. The mAbs were then evaluated by antigenic ELISA for the detection of forty-six FMDV serotype O isolates representing seven of ten known topotypes. Isolates ECU/4/10 and HKN/2/11 demonstrated the highest antigenic variation compared to the others. Furthermore, the panel of mAbs was used in vaccine matching by antigenic profiling ELISA with O1/Manisa as the reference strain. However, there was no correlation between vaccine matching by antigenic ELISA and the gold standard method, virus neutralisation test (VNT), for the forty-six FMDV/O isolates. Nine isolates had particularly poor correlation with the reference vaccine strain as revealed by the low r1 values in VNT. The amino acid sequences of the outer capsid proteins for these nine isolates were analyzed and compared with the vaccine strain O1/Manisa. The isolate ECU/4/10 displayed three unique amino acid substitutions around the antigenic sites 1, 3 and 4.

Conclusions: The panel of mAbs is useful to monitor the emergence of antigenically different strains and determination of relevant antigenic site differences. However, for vaccine matching VNT remains the preferred method but a combination of VNT, antigenic profiling with a panel of mAbs and genetic sequencing would probably be more ideal for full characterization of any new outbreak isolates as well as for selection of vaccine strains from FMDV antigen banks.

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Localization of antigenic sites in FMDV/O capsid proteins. The O1/ BFS1860 crystal structure (PDB # 1FOD) was manipulated with Chimera and shown in surface format. a. Locations of previously identified 5 antigenic sites; b. Locations of identified epitopes of anti-FMDV/O mAbs (summarized in Table 1) showing in red. For VP1 residues 211-213: no corresponding structure in 1FOD (FMDV/O1/ BFS1860 crystal structure).
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Figure 2: Localization of antigenic sites in FMDV/O capsid proteins. The O1/ BFS1860 crystal structure (PDB # 1FOD) was manipulated with Chimera and shown in surface format. a. Locations of previously identified 5 antigenic sites; b. Locations of identified epitopes of anti-FMDV/O mAbs (summarized in Table 1) showing in red. For VP1 residues 211-213: no corresponding structure in 1FOD (FMDV/O1/ BFS1860 crystal structure).

Mentions: The five mutant sequences of P1 gene encoding capsid proteins (VP1, VP2, VP3 and VP4) were compared with parental O/BFS P1 gene. Mutants are named based on their matching mAbs. The sequence data revealed that two selected mutants with the mAbs F21-34 and F21-58 recognized antigenic site 2 in the region of VP2 amino acid positions about 68 and 77, respectively (Table 1). The mutant selected with mAbs F21-41 was found to recognize antigenic site 3 at VP1 amino acid positions close to 43-44, whereas the mutant selected with F21 -18 recognized near antigenic site 4 at amino acid position about 59 located in VP3. The mAb F21-48 recognized antigenic site1a on the GH loop of VP1 at amino acid position 148 (Table 1). The FMDV/O antigenic sites1a (site 5), 1b, 2, 3 and 4 identified in this study were similar as previously published [11,19,20]. The locations of mAb binding sites are shown in the FMDV 3D structure (Figure 2).


Characterization of monoclonal antibodies against foot-and-mouth disease virus serotype O and application in identification of antigenic variation in relation to vaccine strain selection.

Yang M, Xu W, Goolia M, Zhang Z - Virol. J. (2014)

Localization of antigenic sites in FMDV/O capsid proteins. The O1/ BFS1860 crystal structure (PDB # 1FOD) was manipulated with Chimera and shown in surface format. a. Locations of previously identified 5 antigenic sites; b. Locations of identified epitopes of anti-FMDV/O mAbs (summarized in Table 1) showing in red. For VP1 residues 211-213: no corresponding structure in 1FOD (FMDV/O1/ BFS1860 crystal structure).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4125342&req=5

Figure 2: Localization of antigenic sites in FMDV/O capsid proteins. The O1/ BFS1860 crystal structure (PDB # 1FOD) was manipulated with Chimera and shown in surface format. a. Locations of previously identified 5 antigenic sites; b. Locations of identified epitopes of anti-FMDV/O mAbs (summarized in Table 1) showing in red. For VP1 residues 211-213: no corresponding structure in 1FOD (FMDV/O1/ BFS1860 crystal structure).
Mentions: The five mutant sequences of P1 gene encoding capsid proteins (VP1, VP2, VP3 and VP4) were compared with parental O/BFS P1 gene. Mutants are named based on their matching mAbs. The sequence data revealed that two selected mutants with the mAbs F21-34 and F21-58 recognized antigenic site 2 in the region of VP2 amino acid positions about 68 and 77, respectively (Table 1). The mutant selected with mAbs F21-41 was found to recognize antigenic site 3 at VP1 amino acid positions close to 43-44, whereas the mutant selected with F21 -18 recognized near antigenic site 4 at amino acid position about 59 located in VP3. The mAb F21-48 recognized antigenic site1a on the GH loop of VP1 at amino acid position 148 (Table 1). The FMDV/O antigenic sites1a (site 5), 1b, 2, 3 and 4 identified in this study were similar as previously published [11,19,20]. The locations of mAb binding sites are shown in the FMDV 3D structure (Figure 2).

Bottom Line: Isolates ECU/4/10 and HKN/2/11 demonstrated the highest antigenic variation compared to the others.The amino acid sequences of the outer capsid proteins for these nine isolates were analyzed and compared with the vaccine strain O1/Manisa.However, for vaccine matching VNT remains the preferred method but a combination of VNT, antigenic profiling with a panel of mAbs and genetic sequencing would probably be more ideal for full characterization of any new outbreak isolates as well as for selection of vaccine strains from FMDV antigen banks.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Centre for Foreign Animal Disease, 1015 Arlington Street, Winnipeg R3E 3 M4, Manitoba, Canada. Ming.Yang@inspection.gc.ca.

ABSTRACT

Background: Foot-and-mouth disease (FMD) has severe implications for animal farming which leads to considerable financial losses because of its rapid spread, high morbidity and loss of productivity. For these reasons, the use of vaccine is often favoured to prevent and control FMD. Selection of the proper vaccine is extremely difficult because of the antigenic variation within FMDV serotypes. The aim of the current study was to produce a panel of mAbs and use it for the characterization of new isolates of FMDV serotype O.

Results: A panel of FMDV/O specific mAb was produced. The generated mAbs were then characterized using the peptide array and mAb resistant mutant selection. Seven out of the nine mAbs reacted with five known antigenic sites, thus the other two mAbs against non-neutralizing sites were identified. The mAbs were then evaluated by antigenic ELISA for the detection of forty-six FMDV serotype O isolates representing seven of ten known topotypes. Isolates ECU/4/10 and HKN/2/11 demonstrated the highest antigenic variation compared to the others. Furthermore, the panel of mAbs was used in vaccine matching by antigenic profiling ELISA with O1/Manisa as the reference strain. However, there was no correlation between vaccine matching by antigenic ELISA and the gold standard method, virus neutralisation test (VNT), for the forty-six FMDV/O isolates. Nine isolates had particularly poor correlation with the reference vaccine strain as revealed by the low r1 values in VNT. The amino acid sequences of the outer capsid proteins for these nine isolates were analyzed and compared with the vaccine strain O1/Manisa. The isolate ECU/4/10 displayed three unique amino acid substitutions around the antigenic sites 1, 3 and 4.

Conclusions: The panel of mAbs is useful to monitor the emergence of antigenically different strains and determination of relevant antigenic site differences. However, for vaccine matching VNT remains the preferred method but a combination of VNT, antigenic profiling with a panel of mAbs and genetic sequencing would probably be more ideal for full characterization of any new outbreak isolates as well as for selection of vaccine strains from FMDV antigen banks.

Show MeSH
Related in: MedlinePlus